Drugs to Treat Endocrine Problems

7/29/2019 Drugs to Treat Endocrine Problems

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DRUGS TO TREAT ENDOCRINE PROBLEMS

Endocrine System:

Regulates the following:

Reproduction

Growth

Immunity

Energy

Fluid, electrolyte and acid base balance

Maintains Homeostasis

helps all other organs to function properly

Organs of the Endocrine System:

Small ductless glands

Dispersed throughout the body

Produce HORMONES

Hormones: Chemical messengers

Secreted into the bloodstream

Carried by the blood

Bind to specific receptors of target cells to alter cellular activities

Homeostatic Feedback Mechanism:

Negative Feedback Mechanism decreases deviation from normal

Positive Feedback Mechanism increases deviation from normal

Hypothalamus:

GRACE ANN L. LAGURA, RN MAN Page 1


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Regulates endocrine function

Between brainstem and cerebrum

Releases hormones:

Growth Hormone Releasing Hormone

Thyrotropin Releasing Hormone

Corticotropin Releasing Hormone

Gonadotropin Releasing Hormone Prolactin Releasing Hormone

Major Organs of the Endrocrine System:

Pituitary Gland

Thyroid Gland

Parathyroid Gland

Pancreas

Adrenal Glands

Gonads

Pineal Gland Thymus

Pituitary Gland:

Known as the Master Gland

Pituitary hormones direct the activity of all other endocrine organs

Located below the hypothalamus

Infindibulum connects the pituitary gland to the hypothalamus

2 Regions:

Posterior Lobe

made up of nerve fibers storage area of 2 hormones produced by the hypothalamus:

Oxytocin initiates uterine contraction

Antidiuretic Hormone (ADH) also known as

Vasopressin; stimulate reabsorption of water from thecollecting tubules

Anterior Lobe

Glandular tissue

produce Tropic Hormones

Somatotrophs

Thyrotrophs

Carticotrophs

Lactotrophs

Gonadotrophs

Melanocyte Stimulating Hormone

Anterior Pituitary Hormones:


Somatotrophs

Growth Hormones (GH)

ThyrotrophsThyroid Stimulating Hormone

(TSH)


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(

Growth Hormones:

Stimulates growth in bone and muscles

Decreased GH = Dwarfism

Increased GH = Gigantism

Increased GH in adults = Acromegaly (abnormally large hands, feet and facial features)

Thyroid Gland:

Butterfly-shaped organ located in the neck

Anterior or infront of the trachea

Secrete:

thyroid hormones (T3 and T4) - Increased oxygen consumption of most of

thebody cells

Thyrocalcitonin regulates calcium

Parathyroid Gland:

4 Tiny glands embedded at the back of the thyroid

Secrete Parathyroid Hormone (PTH) important in calcium and phosphate regulation

Adrenal Glands:

Triangular glands at the top of each kidney

2 endocrine glands:

Outer adrenal cortex

Glucocorticoids Mineralocorticoids

Androgens

Inner adrenal medulla

Catecholamines epinephrine and norepinephrine

Pancreas:

Located near the duodenum of the intestines

Aids in digestion

Produce hormones: regulates glucose in the body

Insulin beta cells Glucagon alpha cells

Somatostatin delta cells


Corticotrophs

AdrenocorticotrophicHormone

(ACTH)

GonadotrophsFollicle Stimulating Hormone (FSH)

And Luteinizing Hormone (LH)

Lactotrophs

Prolactin


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Gonads:

Produce sex hormones regulate reproductive functions

Females gonads are called ovaries

estrogen and progesterone

Males gonads are called testes

androgens; testosterone (most important male androgen) by Leydigcells

Thymus Gland:

Located posterior or behind the sternum

Regresses with age

2 major hormones: help T-lymphocytes mature (immune system)

Thymosin

Thymopoietin

Pineal Gland:

Secrete and synthesize Melatonin almost entirely at night Melatonin affects the functions of the thyroid, adrenal and gonads

DRUGS FOR DIABETES MELLITUS

DIABETES MELLITUS

Chronic metabolic disorder resulting from insufficient secetion of insulin

Disorder of carbohydrate metabolism

Signs and symptoms of Diabetes Mellitus result from:

insulin insulinPrinciple Sign: Sustained Hyperglycemia

Polyuria

Polydipsia

Polyphagia

Ketonuria

Weight loss

May lead to:

Hypertension

Cardiac diseases

Renal failure

Neuropathy

Amputations

Impotence

stroke

TYPE 1 (IDDM) TYPE 2 (NIDDM)

Juvenile onset diabetes

Develops during childhood and

adolescents

Signs and symptoms are abrupt

Destruction of pancreatic beta cells

which is responsible for insulinsynthesis

Autoimmune disorder

Cause: COXSACKIE INFECTION

Adult onset diabetes

Almost always with obesity

No ketoacidosis

Insulin may be normal and sometimes

increased

Insulin not proportionate to plasma

glucose level

Release of insulin is delayed



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Peak output of insulin is abnormal

Cause: Familial association

Delayed Insulin Release/Subnormal Peak Output

Resistance of liver, muscles, adipose tissues to insulin

Causes:

receptor binding

number of receptors

receptor responsiveness

Leads to:

Destruction of pancreatic beta cells insulin production

Short term complications of Diabetes Mellitus:

Hyperglycemia when insulin dosage is - when allowed to persist will lead to

KETOACIDOSIS

Hypoglycemia when insulin dosage is

Long term complications of Diabetes Mellitus:

Macrovascular Disease

Hypertension due to atherosclerosis; from a combination ofhyperglycemia

Cardiac diseases and altered lipid metabolism

Stroke

Microvascular Disease

Microangiopathy

basement membrane of capillaries thicken causing a bloodflow

Destruction of small blood vessels cause kidney damage and blindness

(proportionate to the degree and duration of hyperglycemia)

Retinopathy caused by damage to retinal capillaries

Microaneurysms

Scarring and Proliferation Causes local ischemia

Overgrowth of new capillaries vision kill retinal cells

Accelerated by:

Hypertension

Hyperglycemia

smoking

Nephropathy

Proteinuria

glomerular filtration rate

arterial blood pressure



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Common cause of end stage renal disease requires dialysis or kidney transplant Increase incidence in Type 1 than in Type 2 Treatment:

ACEI delay the onset of overt nephropathy and retard

ARBS progression of nephropathy

Neuropathy begins early but usually symptoms are absent for years; related to

sustained hyperglycemia Tingling sensation in the fingers and toes

Pain

Suppression of reflexes

Loss of sensation

Amputations because of severe nerve damage

Impotence caused by combination of blood vessel injury and neuropathy

Gastroparesis injury to the autonomic nerves that control GI motility

Nausea

Vomiting

Delayed gastric emptying

Abdominal distention secondary to atony

DOC: Metoclopramide (Reglan)

Diabetes and Pregnancy:

Disappears after delivery

Contributing Factors:

Placenta produce HPL (anti-insulin enzyme) on the 18 th -20th week AOG

Production of cortisol that promotes hyperglycemia (3X during pregnancy)

blood glucose level (hyperglycemia) from the maternal blood that pass

throughthe placenta to the fetal circulation

Hyperglycemia of the mother will stimulate the production of fetal insulin

whichcauses adverse effects to the fetus

Management:

Blood glucose level must be monitored 6-7X daily

C-section as soon as fetus is matured to be delivered (fetal death usually

occursnear term)

Insulin administration

Diet

Diagnosing Diabetes:Must be tested in 2 separate days and both must reveal (+) results. Any of the 2 tests

may be employed:

Fasting Plasma Glucose (FPG)

8 hrs after the last meal

Normal Value: 60-110 mg/dl

Casual Plasma Glucose Test

Blood is drawn anytime

Fasting not required 200 mg/dl and is (+) of DM but must exhibit signs and symptoms

Oral Glucose Tolerance Test (OGTT)

DM is suspected but FPG and Casual Plasma Glucose is not definite

Give oral glucose load of 75 grams Anhydrous Glucose and measure plasma

glucose 2 hrs later

200 mg/dl and = (+) DM



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Not used for routine screening

Treatment:

Diet

Proper diet balance because Type 1 individuals are thin

Carbohydrates 60 to 70% of daily energy intake

Proteins 15 to 20% space evenly

Polysaturated fats 10% throughout

Saturated fats -


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RBC lifespan is 120 days reflect average glucose levels over 2-3 months

Provide a picture of long term glycemic control

Adjunct to daily glucose monitoring


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Insulin Deficiency Promotes Hyperglycemia By:

glycogenolysis glycogen to glucose

gluconeogenesis CHONS and fats into amino acids

glucose utilization

Insulin is Indicated to Patients With:

Type 1 DM

Diabetic Ketoacidosis to allow cells to take up K and lower K level in the blood

Treat hyperkalemia

Types of Insulin:1. Regular (Natural) Insulin

Unmodified crystalline insulin

Rapid onset

Short duration Clear solution

Only form that can be administered IV

Forms aggregates if given SC

Given 30-60 minutes AC

2. Lispro Insulin (Humalog)

Acts faster than Natural Insulin

Shorter duration: 3-6 hours

Rapid acting: 15-30 minutes

Can be given AC and even PC

Dispense by prescription

Because of its short duration, must be given with Intermediate or Long Acting Insulin

To provide basal glycemic control between meals and during the night

3. Insulin Aspart (Novolog)

Analog of human insulin

Short duration: 3-5 hours

Rapid Onset: 10-20 minutes

Available in 10 ml vials

Given SC eat within 5-10 minutes immediately after administration

In combination with Immediate or Long Acting Insulin to provide basal glycemic

control between meals and at night

Can be mixed with NPH mixing is done just before administration

Dispense by prescription

4. Neutral Protamine Hagedorn (NPH) Insulin

Protamine the solubility of NPH; retards absorption

Delayed Onset

Extended duration

Intermediate acting

Protamine is a foreign body watch for allergic reactions

5. Lente Insulin and Ultralente Insulin less allergenic than NPH

Semilente Insulin

Most rapid



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Amorphous; noncrystalline

Small particles of small size

Ultralente Insulin

Large crystals

Dissoleve slowly

Long duration of action

Lente Insulin 70% ultralente

30% semilente

Intermediate duration of action

6. Insulin Glargine (Lantus)

Modified human insulin

Prolonged duration of action: 24 hours

SC OD for children with Type 1 and adults with Type 2

Low solubility at physiologic ph

SC produces microprecipitates that slowly dissolve and release insulin in small amounts

over a prolonged time Blood levels of Glargine is steady in 24 hours

Less risk of hyperglycemia or hypoglycemia

Clear solution but not mixed with any other insulins and not given IV

Administration and Storage:

Available in 100 u/ml

500 u/ml per request for emergencies and patients with severe insulin resistance

400 u/ml available in other countries

All insulins are given SC

Only regular insulins can be given IM, IV IM if IV is ompossible

IV insulin can be absorbed in the administration set which the dose

received

Preparation:

Insulin preparations consist of particles, they must be evenly mixed

Roll the vial between the palms gently vigorous rolling can cause frothing

Sites:

Upper arms - injections must be made in only one general locale to prevent

Thighs lipohypertrophy

Abdomen - 1 inch between sites; site is only used once a month

Compatibility of SA Insulins with LA Insulins:

SA INSULINS

LONG ACTING INSULINS

NPH LENTE ULTRALENTE GLARGINE

Regular Yes Yes Yes -----

Lispro Yes Yes Yes -----

Aspart Yes ----- ----- -----


CLEAR Regular Insulin

Lispro

Glargine

CLOUDY Aspart

Lente

NPH

Ultralente


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Storage:

Unopened Vials

Refrigerated until needed

Can be used up to the expiration date

Vials in Current Use

Kept at room temperature for 1 month

Causes less pain than injecting cold insulin

Partially-Filled Vials

Discarded after several weeks if they are unused

Mixtures of Insulin Prepared in Vials

Stable for 1 month at room temperature

3 months under refrigeration

Mixtures of Insulins at Pre-Filled Syringe

Refrigerated with the needle facing up to avoid clogging

Methods of Insulin Delivery:

Jet Injectors

Shoot insulin through the skin

No use of needle

Pen Injectors

With disposable needle and disposable insulin-filled cartridge

Insulin Pumps

Computerized device deliver basal infusion of insulin (Regular, Lipro, Aspart)

Plus bolus doses before each meal

Matches the patients metabolism

Implantable Insulin Pumps

Surgically implanted in the abdomen

Delivers insulin intraperitoneally or IV

Intranasal Insulin

Rapid onset

Brief duration

Suitable for delivery of mealtime insulin supplement

Cant meet basal insulin needs

10% is absorbed

INSULIN THERAPY OF DM:

Given to all Type 1 to maintain acceptable level of blood glucose

Given to some patients with Type 2

Given to Gestational Diabetes

Referred to as TIGHT GLUCOSEMONITORING

Tight Glucose Monitoring:Benefits:

microvascular complications in total diabetes end points

Drawbacks:

Hypoglycemia because glucose levels are kept relatively low

Weight gain



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Dosage:

Must match with insulin needs

caloric meals - insulin dosage

Special needs to increase insulin:

Infection

Stress

Obesity

Adolescent growth

Needs to Insulin:

Exercise

Pregnancy (during the 1st trimester)

Complications of Insulin Therapy:

Blood glucose of


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SulfonylureasBeta blockersAlcoholMeglitinides

Hyperglycemic Agents drugs that increase blood sugar level

Examples:Thiazides

GlucocorticoidsSympathomimetics

Beta Blockers

delay awareness of insulin-induced hypoglycemia by masking signs associated

withSNS stimulation

impairs glycogenolysis a way for our body to counteract glucose level

ORAL HYPOGLYCEMICS FOR TYPE 2 DM:

indicated only for Type 2 DM

used only when diet and exercise failed to produce glycemic control

1. Sulfonylureas

promote insulin release

derivatives of sulfonamides but no antimicrobial effects

1st Generation 2nd Generation

Less potent

Drugs:

Tolbutamide

Acetohexamide

Tolazamide

Chlorpropamide

More potentWill need a lower dosageDrugs:

Glipizide

Glyburide

Glimepiride

Example:TOLBUTAMIDE (Orinase)

First generation Stimulate the release of insulin from the pancreas

If pancreas is unable to synthesize insulin Tolbutamide if ineffective

Not effective in Type 1 DM; with prolonged use may cellular sensitivity to

insulin

Tolbutamide binds and blocks with K channels Glucose-dependent

Increase influx of calcium

Release of Insulin

Adverse Effects of Tolbutamide:

Hypoglycemia may be severe and require dextrose infusion

Teratogenic in pregnancy

Cardiovascular toxicity

2. Meglitinides



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Same as sulfonylureas

Stimulates release of pancreatic enzymes

Example:REPAGLINIDE blocks K channels, increase calcium influx, increase insulin

Adverse Effects of Repaglinide:

Hypoglycemia patients should not eat later than 30 minutes

3. BiguanidesExample:

METFORMIN (Glucophage)

production of glucose by the liver

Suppressionof gluconeogenesis

Enhances glucose uptake and utilization by the muscles Do not promote insulin release by the pancreas

Do not cause hypoglycemia

Given PO absorbed slowly by the small intestines

Excreted in the kidneys unchanged - kidney function result to toxicity

Side Effects:

appetite

Nausea and vomiting

absorption of vitamin B12 and folic acid

Weight loss

Toxicity: Lactic acidosis medical emergency

Myalgia

Hyperventilation hemodialysis is done to remove Metformin

Malaise

Somnolence

4. Thiazolinediones (Glitazones)

glucose level by decreasing insulin resistance

the ability of the target cells to respond to insulin

Used as a monotherapyDrugs:

Rosiglitazone 4 mg/day to plasma glucose by 76 mg/dl

Pioglitazone

Troglitazone

Adverse Effects:

Fluid retention

Edema

Weight gain

Mixed Effects on Plasma Lipid Panels:

LDL bad HDL good

triglycerides good

Monitoring:

Liver function tests drug is hepatotoxic

Check ALT before starting treatment



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5. Alpha Glucosidase Inhibitors:

Delay absorption of dietary CHO

blood glucose after meals

postprandial rise in blood glucose

For hyperglycemia not controlled by diet or exercise

Used alone or in combination with insulin, metformin or sulfonylureas

Drugs:

Acarbose (Precose)

Miglitol

Adverse Effects: caused by bacterial fermentation of unabsorbed CHO

Flatulence

Cramps Abdominal distention

Borborygmus (rumbling bowel sounds)

diarrhea

AcarboseInsulin if combined, can cause hypoglycemiaSulfonylureas

DIABETIC KETOACIDOSIS:Most severe manifestation of insulin


Insulin

Altered Fat Metabolism Altered Glucose Metabolism

Lipolysis

FFA

Glycerol(substrate forglucosesynthesis)

Glucoseproduction

GlucoseMetabolism

Hyperglycemia

Glycosuria (more than thereuptake of the glomeruli)

FFA Oxidation inthe liver

Ketoacids

Ketosis (detected by theodor of decayed apples in

OsmoticDiuresis

Vomiting

Water, Na, K loss


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Diabetic Ketoacidosis:

brought by altered glucose and fat metabolism

altered glucose metabolism cause hyperglycemia, water loss and hemoconcentration

altered fat metabolism cause production of ketoacids

Treatment of Ketoacidosis:

Restoration of Insulin Levels

IV bolus of insulin

0.1 u/kg BW

Correction of Acidosis

Given with HCO3 44.6 mEq dissolve in 500 ml of 0.45% Saline

Infused over 1 hour

Give K also because HCO3 promoted hypokalemia

Replacement of water and sodium

IV saline 0.9% or 0.45%

Adults require 8-10 L for the first 12 hours

K Replacement

If plasma K is normal, K should not be administered until plasma level inresponse

to insulin

If plasma K is low, K must be given ASAP

Glucose Normalization

Treat ketoacidosis with insulin will cause hypoglycemia

In case of hypoglycemia give glucagon or glucose itself

Glucagon for Insulin Overdose:Glucagon

A hormone produce by alpha cells of the pancreatic islets

plasma level of glucose

Relaxes smooth muscles of the digestive tract

blood glucose levels after insulin overdose

Promotes breakdown of glycogen


KetoacidosisAegh erventilates

SHOCK

Dehydration

Hemoconcentration


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DRUGS FOR THYROID DISORDERS

Thyroid Gland:

Produce 2 active hormones:

Triiodothyronine (T3) 3 atoms of iodine

Thyroxine (T4) 4 atoms of iodine

Thyroid Hormone Actions:3 Principal Actions:

Stimulation of energy use

Elevates basal metabolic rate

Increased oxygen consumption

Increased heat production

Stimulation of the heart

Increases rate and force of contraction

Increased cardiac output

Increased oxygen demand

Promotion of growth and development Essential for the normal development of the brain and other components

of thenervous system

Maturation of skeletal muscles

Synthesis and Fate of Thyroid Hormones:Step 1

Formation of thyroid hormones through the uptake of iodide into the thyroid

Uptake process produce 20-50X greater than plasma iodide concentrations

Step 2

Oxidation

IodideBy the enzyme Peroxidase

Iodine (active form of iodide)Step 3

Iodine becomes incorporated into tyrosine residues that are bound to

thyroglobulin

One tyrosine molecule may receive 2 or more iodine atoms

Resulting in the production of MonoiodityrosineAnd Diiodotyrosine

Step 4

Iodinated tyrosine molecules are coupled

Diiodotyrosine + Monoiodityrosine = T3

Diiodotyrosine + Diiodotyrosine = T4

Fate:



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Thyroid hormones are released from the thyroid by proteolytic process

Release of T4 is greater than the release of T3

T4 undergoes conversion to T3 by enzymes in the periphery

The conversion of T4 to T3 accounts for 80% of the T3 found in the plasma

99.5% of the T3 and T4 are bound to plasma

Only a small percentage of the circulating thyroid hormones are free to cause biologic

effects

thyroid hormones are excreted by hepatic metabolism metabolism takes place slowly

because they are bound to proteins

T of T3 = 1.5 days

T of T4 = 1 week

Regulation of Thyroid Function by the Hypothalamus and Anterior Pituitary Gland:

Hypothalamus

Thyrotropin Releasing Hormone (TRH)

Anterior Pituitary Gland

Thyroid Stimulating Hormone (TSH)

Thyroid

Inhibition

T3 & T4

Biologic Effects

Influence of Iodine Levels on Thyroid Function:

Low Iodine

Causes in thyroid hormones

Promotes release of TSH

Thyroid size increases (goiter)Thyroid increases its concentration of iodine

High Iodine

Uptake of iodide is suppressed

Synthesis and release of thyroid hormones



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HYPOTHYROIDISM:

Can occur at any age

Deficiency of thyroid hormones

Mild deficiency hypothyroidism

Severe deficiency myxedema

Hypothyroidism in infants called cretinism

Hypothyroidism in Adults:Signs & Symptoms:

Pale, puffy and expressionless face Skin is cold and dry

Brittle hair; hair loss

HR

temperature

Lethargy, fatigue

Cold intolerance

Mental impairment

Goiter (due to overstimulation of TSH)

Causes:

Impaired thyroid gland

Hashimotos disease autoimmune thyroiditis

Insufficient iodine in the diet

Surgical removal of the thyroid

Destruction of the thyroid by radioactive iodine

Insufficient secretion of TSH and TRH

Treatment:

Levothyroxine (T4) alone usually lifetime

Levothyroxin + Liothyronine may be superior

Hypothyroidism During Pregnancy:

Maternal hypothyroidism- can cause congenital hypothyroidism

Congenital hypothyroidism can cause mental retardation and developmental problems

Maternal hypothyroidism has impact largely on the 1st trimester when the fetus is unable

to produce thyroid hormones

Maternal hypothyroidism must be diagnosed early or as soon as pregnancy is confirmed

to start treatment immediately

Thyroid level should be monitored and dosage increase as needed

Hypothyroidism in Infants:Signs & Symptoms:

Mental retardation

Derangement of growth Large and protruding tongue

Potbelly

Dwarfism

Impaired development of nervous system, bones, teeth and muscles

Causes:

Autoimmune disease



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Severe iodine deficiency

TSH deficiency

Exposure to radioactive iodine in utero

Treatment:

Replacement therapy within a few days after birth and continue for life

Thyroid Hormone Preparations for Hypothyroidism:

Available as pure, synthetic compounds

Extracts of animal thyroid glands

Levothyroxine (T4)

Levothyroxine (Levothroid, Levoxyl, Synthroid, Unithroid)

DOC for most patients

The drug is converted to T3

Produce nearly normal levels of T3 and T4

No need to give T3 along with Levothyroxine

T of 7 days

Because of long half life, onset is delayed

Because of long half life, it causes hormone levels to remain steady between doses

Permits OD dosing

Given life time

Indications:

All forms of hypothyroidism (secondary to TSH and TRH) Cretinism

Myxedema coma

Ordinary hypothyroidism in adults and children

Simple goiter

Maintain proper levels of thyroid hormones following thyroid surgery,

irradiation and treatment with antithyroid drugs

Should not be taken to treat obesity (will accelerate metabolism and promote

weight reduction if the drugs are taken high enough to establish hyperthyroidstate)

Adverse Effects:

Thyrotoxicosis

Drug Interaction:

Dosage and Administration:

Routes of administration


Drugs that LevothyroxineAbsorption:

Cholestyramine (Questran)

Colestipol (Colestid)

Ca supplements

Sucralfate

Aluminum-containingantacids

Iron supplements

Space administration by 3-4

Drugs that LevothyroxineMetabolism:

Phenytoin (Dilantin)

Carbamazepine (Tegretol)

Rifampicin (Rifadin)

Phenobarbital


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Oral is taken on an empty stomach

Taken in the morning before breakfast

IV is used for myxedema coma

IV doses are of the size of oral doses

HYPERTHYROIDISM:2 Forms:

Thyroid Function Tests:

Serum T4 Test


GRAVES DISEASE most common cause of thyroid

hormone excretion

Incidence: females 20-40 years oldS/S:

Rapid and strong HR

Dysrhythmias

Angina

Rapid thought flow

Rapid speech

Nervousness

Insomnia

Weak skeletal muscles; may atrophy

metabolic rate heat production; temp heat

intolerant

Warm and moist skin

appetite

Weight loss (if caloric intake fails to

match metabolic rate)

Exophthalmos

Collective signs indicate Thyrotoxicosis

Cause:

Thyroid stimulation is caused by

thyroid-stimulating immunoglobulins(TSIs) antibodies produced byautoimmune process

TSIs stimulate TSH

Treatment:

Surgical removal of the thyroid

Radioactive iodine to destroy thyroid

tissue Antithyroid drugs

- Propylthiouracil- Methimazole

Propanolol to treat tachycardia

Exophthalmos is not a result ofhyperthyroidism per se, it is treated withlucocorticoids

PLUMMERS DISEASE (ToxicNodular Goiter)

Result of thyroid adenoma

Persistent condition Rarely with remission

S/S:

Similar with Graves disease but

without exophthalmos

Treatment:

Antithyroid drugs symptoms

return rapidly when drug is d/c

Surgery

radiation

THYROTOXIC CRISIS Extremely high thyroid levels

Characterized By:

- hyperthermia- tachycardia- weakness- heart failure- coma

Cause:

excessive production ofthyroidhormones

overdose of thyroid hormone

replacementTreatment:

KI

Iodine solution

PTU

Propanolol to reduce

tachycardia


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Measures total thyroxine

Reflects overall thyroid activity

For initial screening of thyroid function

Hypothyroidism: T4 level

Hyperthyroidism: T4 level

Used to monitor thyroid hormone replacement therapy

All thyroid preparations except Liothyronine should increase T4 level

Serum T3 Test

Measures total triiodothyronine

Effective in diagnosing hyperthyroidism (because in hyperthyroidism, T3 often

risesooner and in greater extent than in T4

All thyroid preparations increase T3

Serum TSH

Most sensitive method of diagnosing hypothyroidism

Because very small reductions in T3 and T4 cause dramatic rise of TSH

Used to distinguish primary hypothyroidism from secondary hypothyroidism

Primary thyroidal; TSH levels are very high

Secondary hypothyroidism from anterior pituitary dysfunction; TSH levels

are very lowDrugs for Hyperthyroidism:

Propylthiouracil (PTU)Methimazole (Tapazole)

Blocks thyroid hormone synthesis

Prevents oxidation of iodide, inhibiting incorporation of iodine into tyrosine

Prevents iodinated tyrosines from coupling

Inhibits Peroxidase (the enzyme that catalyzes both reactions)

Acts in the periphery to prevent the conversion of T4 to T3

Does not destroy existing stores of thyroid hormones

Takes about 3-4 weeks to produce euthyroid state

Given oral

Rapid onset within 30 minutes

T is 75 minutes drug can be given several times a day

Crosses placental barrier and breastmilk

Indications:4 Applications in Hyperthyroidism:

PTU can be used alone for Graves disease

As an adjunct to radiation therapy - to control hyperthyroidism until the effects

of radiation appear

Suppress thyroid hormone synthesis in preparation for thyroid surgery

For thyrotoxicosis

Adverse Effects:

Agranulocytosis

develops during the 1st 2 months

sorethroat and fever earliest signs

PTU must be discontinued

Treated with Granulocyte-stimulating factor (Neupogen)

Hypothyroidism

Neonatal hypothyroidism and goiter dosage must be kept low

Radioactive Iodine (131I)Iodine 131 (Iodotope)

T of 8 days



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Used in Graves disease destroy thyroid tissue in hyperthyroidism

Beta particles emitted by the gamma rays of the 131I do not travel outside the thyroid

Initial effects appear in days or weeks

Full effects in 2-3 months

Who Should Be Treated With Radioactive Iodine?

Patients over the age of 30

Non responsive to other antithyroid drugs

Non responsive to subtotal thyroidectomy

Who Should Not Be Treated with Radioactive Iodine?

Children because of delayed hypothyroidism

Pregnant mothers Nursing mothers

Dosage:

Determined by the thyroid size

4-10 millicuries (mCi)

Use in Thyroid Cancer:

Destroy malignant thyroid cells

But all forms of thyroid cancer do not accumulate iodine

Must give large doses

Severe adverse effects:

- leucopenia- thrombocytopenia- anemia

Preparations:

available in capsules and solutions

odorless and tasteless

Nonradioactive Iodine

Strong Iodine Solution (Lugols solution)

Sodium Iodide (IV)

Potassium Iodide

Action: High concentrations produce paradoxical suppressant effect on the thyroid

Decrease iodine uptake by the thyroid

Inhibit thyroid hormone synthesis

Decrease circulating T3 and T4

Propanolol (Inderal)

Suppress tachycardia and other symptoms of Graves disease

Occur rapidly unlike Methimazole and PTU

All patients must receive Propanolol unless contraindicated


ADVANTAGES:

Low cost

Spared the risk, discomfort and expenseof thyroid surgery

Death is less likely to occur

No other tissue is injured

DISADVANTAGES:

Effect of treatment is delayed

Treatment is associated with

delayed hypothyroidism


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DRUGS RELATED TO HYPOTHALAMIC & PITUITARY FUNCTION

Pituitary Gland situated just below the brainHypothalamus located above the pituitary gland

2 Divisions of the Pituitary Gland: Anterior Pituitary or adenohypophysis

Posterior Pituitary Gland or neurohypophysisHormones of the APG:

Production & release is controlled by the hypothalamus. Growth Hormone (GH) stimulates growth of all tissues and organs Corticotropin (ACTH) acts on the adrenal cortex Thyrotropin (TSH) acts on the thyroid gland Follicle Stimulating Hormone (FSH) acts on the ovaries to promote follicular growth

& development and in the testes to promote spermatogenesis Luteininzing Hormone (LH)

promote ovulation and development of corpus luteum in women In men, LH is known as Interstitial cell-stimulating hormone (ICSH) acts on

thetestes to promote androgen production

Prolactin stimulates milk production after parturitionHormones of the PPG:

Hormones are synthesize in the hypothalamus & stored at the PPG

Oxytocin facilitate uterine contraction at birth

ADH promote renal conservation of water

Hypothalamus Release-Regulating Factors:

Gonadotropin Releasing Hormone (GnRH)

Growth Hormone Releasing Hormone (GHRH)

Prolactin Releasing Hormone (PRH)

Corticotropin releasing Hormone (CRH)

Thyrotropin Releasing Hormone (TRH)

Somatostatin

Dopamine

Feedback Regulation of the Hypothalamus and the APG:

Regulated by negative feedback mechanism


Hypothalamu

Releasing Factor

Anterior Pituitary

Hormone A


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Biologic EffectsBiologic Effects:

Promotion of Growth

Stimulate growth of all organs and tissues

Must be administered prior to epiphyseal closure

GH increase bone length producing increase in height

Result in enlargement of muscle mass

Organs grow proportionate to body growth

Brain and eyes do not respond to GH

Promotion of Protein Synthesis

Cells must increase production of protein GH increase amino acid uptake and utilization

Increased protein synthesis result to increase net nitrogen retention (because

aminoacids have nitrogen content)

May result in reduce urinary nitrogen excretion

Result to decreased BUN

Effects of Carbohydrate Metabolism

Reduce glucose utilization; plasma glucose level increase

When GH is given to nondiabetics, elevation of blood glucose stimulates the

releaseof insulin

When GH is given to diabetic patients, insulin is not released, hyperglycemic

actionof GH is unopposed

Growth Hormone Deficiency

GH in children result in Dwarfism

Growth is retarded to an equal extent in all parts of the body

Cause is primarily pituitary adenoma

Dwarfism is not associated with mental impairment

Growth of normal individuals cease at puberty Dwarves continue to grow throughout life

Treatment: replacement therapy with human GH

Growth Hormone Excess

GH in children result in Gigantism (Giantism); children grow very tall

In adults, it is Acromegaly; result in coarse facial features, splayed teeth, large hands

and feet; height is not increased due to closure of epiphyses

Signs:

Cardiomegaly

Hypertension Arthralgias

Hyperglycemia

Headache

Treatment:

Surgical removal of the pituitary then radiation as an adjunct treatment


Target organ

Hormone B


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Radiation as a primary treatment may take 10-20 years to produce full response

Octreotide (Sandostatin)

Analog of somatostatin

Suppress GH release

Mimic suppressant action of somatostatin in the pituitary

Primary therapy for acromegaly or adjunct to radiation and surgery

Usually dose: 100 ug SC TID Side effects: GI upset but may subside of 1-2 weeks, develop

cholesterolGallstones

Therapeutic Uses: For children whose growth has been retarded by growth hormone deficiency Treatment must begin before epiphyseal closure Efficacy of treatment declines as patient grows older and lost at age 20-24 Short children with normal GH level are inappropriate for GH therapy Not very effective for children with normal GH level (average increase in height is

2 in)Adverse Effects:

Hyperglycemia

Hypothyroidism Antibodies to GH

Documents

Drugs to Treat Endocrine Problems